B cells play an important role in HVT vaccine-mediated protection against Marek's disease virus.

Marek's disease virus (MDV) is an alphaherpesvirus that infects chickens, causing immunosuppression, neurological symptoms, and fatal lymphoma. Vaccines are used to protect billions of chickens, but remain poorly understood. To investigate the role of B-cells in vaccine protection, we vaccinated B-cell knockout (JH^-/-) chickens with the commercial HVT vaccine and challenged them with very virulent MDV. Vaccinated JH^-/- chickens showed significantly increased disease incidence and neurological symptoms compared to wild-type siblings, indicating that B-cells contribute to protection against clinical disease. Tumor incidence remained low and comparable to wild-type, suggesting that B-cells are dispensable for preventing tumors. Aside from the absence of B-cells, no major changes in T-cell subsets were detected. Viral genome levels were comparable in the blood and spleen, but elevated in skin and dust in JH^-/- birds early on. These findings reveal that B cells are critical for full HVT vaccine protection and limiting early virus shedding.